This study is designed to address the possible role of altered adrenergic and beta-endorphin activity in premenstrual syndrome (PMS) / premenstrual dysphoric disorder (PDD).After prospective confirmation of diagnosis, 30 women with PMS/PDD and 30 matched controls will undergo multidimensional evaluation of adrenergic function during both the follicular and luteal phases using 24-hour urinary 6-sulphatoxymelatonin, plasma catecholamines at baseline and afterstressors, cardiovascular reactivity to stressors, and cardiovascular responsivity to isoproterenol. Pain sensitivity between PMS and control groups will also be compared at both phases, via determination of ischemic pain threshold and tolerance. Beta-endorphin levels and responsivity of beta-endorphins to stressors and pain stimuli will also be compared. In a second study, 20 of these confirmed PMS/PDD women and 10 controls will participate in a double-blind, randomized crossover comparison of the possible benefits of clonidine (a central alpha-adrenergic agonist with analgesic effects) versus a control treatment with similar perceptible signs (dry mouth). Subjects will take oral medications daily for two menstrual cycles on each treatment, providing daily ratings of physical, emotional, behavioral and pain symptoms. During the second luteal phase on each treatment, the same assessments of adrenergic and beta-endorphin activity and pain sensitivity described above will be made. Thus, this study is expected to provide new insights in regard to the physiological dysregulation involved in PMS and in assessing symptoms alleviated and the mechanisms involved in any improvements associated with clonidine treatment.
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